Unfractionated Heparin Regimen Research Articles

Safety of High-Dose Unfractionated Heparin for Prophylaxis of Venous Thromboembolism in Hospitalized Obese Patients.

Optimal dosing of unfractionated heparin (UFH) for thromboprophylaxis in the obese patient population is uncertain because of their high-risk, prothrombotic state and a complexity of pharmacokinetic considerations. Literature on the appropriateness of the use of a higher dose UFH regimen remains unclear and inconsistent. To evaluate the safety of the use of 7500 units every 8 hours (high-dose) of subcutaneous UFH compared with the use of 5000 units every 8 hours (standard-dose) of subcutaneous UFH for thromboprophylaxis in obese patients (defined as BMI ≥30 kg/m2). In a retrospective cohort study, 326 adult patients were included, with a BMI ≥30 kg/m2, who were admitted to a large, urban academic medical center between September 1, 2015, and September 1, 2018. Patients received either high-dose or standard-dose UFH for at least 48 hours. The primary end point was the incidence rate of bleeding events, defined as a ≥2-g/dL fall in hemoglobin level or receipt of transfusion of 2 or more units of packed red blood cells (pRBCs) from the start of the UFH order. The incidence rate of bleeding was significantly higher in those who received high-dose UFH (43%) compared with those who received standard-dose UFH (29%; P = 0.008). No significant difference was found between venous thromboembolism event rates. High-dose UFH was associated with an increased bleeding event rate compared with standard-dose UFH in patients with a BMI ≥30 kg/m2. This raises safety concerns about the appropriateness of utilizing this regimen in this population.

The effect of heparin infusion intensity on outcomes for bridging hospitalized patients with atrial fibrillation.

BackgroundPerioperative bridging in atrial fibrillation (AF) is associated with low thromboembolic rates but high bleeding rates. Recent guidance cautions the practice of bridging except in high risk patients. However, the practice of bridging varies widely and little data exist regarding appropriate anticoagulation intensity when using intravenous unfractionated heparin (UFH).HypothesisTo determine if high intensity UFH infusion regimens are associated with increased bleeding rates compared to low intensity regimens for bridging patients with AF.MethodsWe conducted a single center retrospective cohort study of admitted patients with non‐valvular AF receiving UFH for ≥24 hours. UFH intensities were chosen at the providers' discretion. The primary endpoint was the rate of bleeding defined by the International Society on Thrombosis and Hemostasis during UFH infusion or within 24 hours of discontinuation. The secondary endpoint was a composite of cardiovascular events, arterial thromboembolism, venous thromboembolism, myocardial infarctions and death during UFH infusion.ResultsA total of 497 patients were included in this analysis. Warfarin was used in 82.1% and direct acting oral anticoagulants in 14.1% of patients. The rate of any bleed was higher among high intensity compared to low intensity UFH regimens (10.5% vs 4.9%, odds ratio = 2.29, 95% confidence interval = 1.07‐4.90). Major bleeding was significantly higher among high intensity compared to low intensity UFH regimens. There was no difference in composite thrombotic events or death.ConclusionsLow intensity UFH infusions, targeting lower anticoagulation targets, were associated with decreased bleeding rates without a signal of increased thromboembolic events in hospitalized AF patients.

Revisiting the Pharmacology of Unfractionated Heparin.

Unfractionated heparin (UFH) is a commonly used anticoagulant therapy for the acute treatment and prevention of thrombosis. Its short duration of action, reversibility of effect by protamine sulfate, and extensive clinical experience are some of the advantages that support its use. However, the choice of dose and dosing regimen of UFH remains challenging for several reasons. First, UFH has a narrow therapeutic window and wide variability in the dose-response relationship. Second, its pharmacodynamic (PD) properties are difficult to characterise owing to the complex multidimensional mechanisms of interaction with the haemostatic system. Third, the complex heterogeneous chemical composition of UFH precludes precise characterisation of its pharmacokinetic (PK) properties. This review provides a comprehensive mechanistic approach to the interaction of UFH with the haemostatic system. The effect of chemical structure on its PK and PD properties is quantitatively described, and a framework for characterisation of the dose-response relationship of UFH for the purpose of dose optimisation is proposed.

Thromboembolic prophylaxis protocol with warfarin after radiofrequency catheter ablation of infarct-related ventricular tachycardia.

Ablation in the left ventricle (LV) is associated with a risk of thromboembolism. There are limited data on the use of specific thromboembolic prophylaxis strategies postablation. We aimed to evaluate a thromboembolic prophylaxis protocol after ventricular tachycardia (VT) ablation. The index procedures of 217 patients undergoing ablation for infarct-related VT with open irrigated-tip catheters were included. Patients with large LV endocardial ablation area (>3cm between ablation lesions) were started on low-dose, slowly escalating unfractionated heparin (UFH) infusion 8hours after access hemostasis, followed by 3months of anticoagulation. Patients with less extensive ablation were treated only with antiplatelet agents postablation. Postablation bridging anticoagulation was used in 181 (83%) patients. Of them, 11 (6%) patients experienced bleeding events (1 required endovascular intervention) and 1 (0.6%) experienced lower extremity arterial embolism requiring vascular surgery. Systemic anticoagulation was prescribed in 190 (89%) of 214 patients discharged from the hospital (warfarin in 98%), while the rest received single- or dual-antiplatelet therapy alone. Patients treated with an anticoagulant had significantly longer radiofrequency time compared to patients treated with antiplatelet agents only. One (0.5%) of the patients treated with oral anticoagulation experienced major bleeding 2 weeks postablation. No thromboembolic events were documented in either the anticoagulation or the "antiplatelet only" group postdischarge. A slowly escalating bridging regimen of UFH, followed by 3months of oral anticoagulation, is associated with low thromboembolic and bleeding risks after infarct-related VT ablation. In the absence of extensive ablation, antiplatelet therapy alone is reasonable.

Real-life experience with a new anticoagulation regimen for patients undergoing left-sided ablation procedures

BackgroundCurrent guidelines for anticoagulation during left-sided procedures recommend the administration of unfractionated heparin (UFH) with an initial bolus of 50–100 U/kg, followed by continuous infusion to maintain an activated clotting time (ACT) ≥ 300 s. Our objective was to compare the effectiveness of this standard regimen (100 U/kg bolus) to a more aggressive approach (200 U/kg bolus). MethodsWe collected data on a series of consecutive patients undergoing left sided ablation procedures. Patients with an INR ≥2.0 on the day of the procedure were excluded. Procedural anticoagulation was performed using one of two UFH regimens: 1) 100 U/kg bolus, followed by 10 U/kg/hour infusion or 2) 200 U/kg bolus, followed by 20 U/kg/hour infusion. ACT was measured 10 min after the second bolus and then controlled every 20 min. Heparin was titrated throughout the procedure to maintain an ACT 300–400 s. Results145 consecutive patients were included in the study: 34 received an initial bolus of 100 U/kg and 111 received 200 U/kg. The mean time required to reach an ACT ≥300 s was 15.25 min (95% CI 12.97–17.03) in the 200 U/kg group and 51.23 min (95% CI 40.65–61.81) in the 100 U/kg group (p < 0.001). There was no difference between groups with regard to thromboembolic or hemorrhagic complications. ConclusionCurrent anticoagulation guidelines for left-sided ablation procedures almost universally fail to achieve an initial ACT ≥300 s. A 200 U/kg heparin bolus is much more effective to promptly reach the target ACT, with a low rate of overshoot.

REAL-LIFE EXPERIENCE WITH A NEW ANTICOAGULATION REGIMEN FOR PATIENTS UNDERGOING LEFT-SIDED ABLATION PROCEDURES

Abstract Background Current guidelines for anticoagulation during left-sided procedures recommend the administration of unfractionated heparin (UFH) with an initial bolus of 50–100 U/kg, followed by continuous infusion to maintain an activated clotting time (ACT) ≥ 300 s. Our objective was to compare the effectiveness of this standard regimen (100 U/kg bolus) to a more aggressive approach (200 U/kg bolus). Methods We collected data on a series of consecutive patients undergoing left sided ablation procedures. Patients with an INR ≥2.0 on the day of the procedure were excluded. Procedural anticoagulation was performed using one of two UFH regimens: 1) 100 U/kg bolus, followed by 10 U/kg/hour infusion or 2) 200 U/kg bolus, followed by 20 U/kg/hour infusion. ACT was measured 10 min after the second bolus and then controlled every 20 min. Heparin was titrated throughout the procedure to maintain an ACT 300–400 s. Results 145 consecutive patients were included in the study: 34 received an initial bolus of 100 U/kg and 111 received 200 U/kg. The mean time required to reach an ACT ≥300 s was 15.25 min (95% CI 12.97–17.03) in the 200 U/kg group and 51.23 min (95% CI 40.65–61.81) in the 100 U/kg group (p Conclusion Current anticoagulation guidelines for left-sided ablation procedures almost universally fail to achieve an initial ACT ≥300 s. A 200 U/kg heparin bolus is much more effective to promptly reach the target ACT, with a low rate of overshoot.

A Prospective Study of Adequacy of Anticoagulation with Fixed Dose Weight Adjusted Unfractionated Heparin in Patients with Deep Vein Thrombosis.

Weight adjusted fixed dose subcutaneous unfractionated heparin (UFH) is one of the options for the treatment of deep vein thrombosis (DVT), but the degree of its anticoagulant effect has not been tested in India. This was a prospective observational study, conducted at a tertiary care hospital in South India between September 2012 and March 2014. DVT was diagnosed using compression ultrasonography. UFH was given as an initial loading dose of 333U/kg followed by a maintenance dose of 250U/kg twice daily subcutaneously. aPTT was done on day 2 and day 4 after 6h of the morning dose of heparin. Patients were categorized based on aPTT ratios. Fifty five patients treated for proximal lower limb DVT had received UFH. Their median age was 41years. DVT was secondary to malignancy, immobilisation or pro-coagulant state. No obvious etiology was found in 47% of the patients. The mean aPTT on day 2 was 41.8s and 51.7s on day 4. The aPTT ratio was subtherapeutic in 63.6% and therapeutic in 32.7% of the patients on day 2. Five patients had adverse events in the hospital. Three patients died and two other patients had confirmed pulmonary embolism. Death was due to pulmonary embolism in one patient and metastatic malignancies in the other two. No bleeding manifestation had occurred. Caution is required in implementing this UFH regimen as this preliminary investigation has found predominantly subtherapeutic aPTT ratios during the initial phase of anticoagulation.

Anticoagulation during and after acute coronary syndrome

Current antithrombotic therapy in patients with acute coronary syndrome (ACS) comprises antiplatelet and anticoagulant therapy. Dual antiplatelet therapy composed of aspirin plus a third generation P2Y12 inhibitor (prasugrel or ticagrelor) represents the gold standard, while aspirin plus second generation P2Y12 inhibitor (clopidogrel) may be used as an alternative in the presence of contraindications for third generation P2Y12 inhibitors and/or a high risk of bleeding. Unfractionated heparin (UFH) has been the unchallenged mainstay in anticoagulation for ACS for many decades and is still widely used in patients with ACS treated interventionally. Novel alternative parenteral anticoagulant strategies include the low molecular weight heparin enoxaparin and the synthetic pentasaccharide fondaparinux. Both of these agents share advantages over UFH particularly in medically treated patients with ACS not scheduled for PCI. The direct parenteral factor IIa (thrombin) inhibitor bivalirudin, when used as sole anticoagulant in patients with ACS undergoing PCI, is as effective as the regimen of UFH plus GPIIb/IIIa inhibitor in NSTEMI and superior to the latter regimen in patients with STEMI. The novel approach of a long-term low dose factor Xa inhibition with rivaroxaban in the post ACS phase even further reduced cardiovascular mortality in a clinical trial but has yet to be established in daily clinical practice in the setting of third generation P2Y12 inhibitors. This review discusses currently clinically established anticoagulants for the treatment of ACS alongside with novel approaches such as rivaroxaban.

Fondaparinux with UnfracTionated heparin dUring Revascularization in Acute coronary syndromes (FUTURA/OASIS 8): A randomized trial of intravenous unfractionated heparin during percutaneous coronary intervention in patients with non–ST-segment elevation acute coronary syndromes initially treated with fondaparinux

There is uncertainty regarding the optimal adjunctive unfractionated heparin (UFH) regimen for percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) treated with fondaparinux. The aim of this study is to evaluate the safety of 2 dose regimens of adjunctive intravenous UFH during PCI in high-risk patients with NSTE-ACS initially treated with fondaparinux and referred for early coronary angiography. This is an international prospective cohort study of approximately 4,000 high-risk patients presenting to hospital with unstable angina or non-ST-segment elevation myocardial infarction, treated with fondaparinux as initial medical therapy, and referred for early coronary angiography with a view to revascularization. Within this cohort, 2,000 patients undergoing PCI will be eligible for enrollment into a double-blind international randomized parallel-group trial evaluating standard activated clotting time (ACT)-guided doses of intravenous UFH versus a non-ACT-guided weight-adjusted low dose. The standard regimen uses an 85-U/kg bolus of UFH if there is no platelet glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitor or 60 U/kg if GpIIb-IIIa inhibitor use is planned, with additional bolus guided by blinded ACT measurements. The low-dose regimen uses a 50 U/kg UFH bolus, irrespective of planned GpIIb-IIIa use. The primary outcome is the composite of peri-PCI major bleeding, minor bleeding, or major vascular access site complications. The assessment of net clinical benefit is a key secondary outcome: it addresses the composite of peri-PCI major bleeding with death, myocardial infarction, or target vessel revascularization at day 30. FUTURA/OASIS 8 will help define the optimal UFH regimen as adjunct to PCI in high-risk NSTE-ACS patients treated with fondaparinux.

Audit of the peri‐delivery use of unfractionated heparin in women on therapeutic low‐molecular weight heparin

There is no evidence-based approach for the optimal management of peri-delivery anticoagulation in women receiving therapeutic dose of low-molecular weight heparin (LMWH) during pregnancy. Nevertheless, the maintenance of anticoagulation for the maximal period peri-delivery appears appropriate in women considered to be at high risk of venous or arterial thromboembolism. We developed a regimen based on fixed thromboprophylactic dose of unfractionated heparin (UFH) peri-delivery and undertook an audit to evaluate the use and feasibility of this approach and any adverse events. Fixed intravenous thromboprophylactic dose of UFH (15,000 units/24 h) was commenced on the evening prior to a planned delivery [induction of labour or elective caesarean section (CS)], stopped 4 h predelivery and restarted 2-6 h postdelivery. Compliance was good with 32/38 consecutive deliveries managed according to the regimen. There were no cases of postpartum haemorrhage and no thrombosis associated with these 32 deliveries. Twenty-one patients were delivered by CS (11 elective) and eight patients received epidural/spinal anaesthesia without complication. In conclusion, the fixed thromboprophylactic dose UFH regimen provided maintenance of anticoagulation except for a matter of hours without excessive bleeding risk (conducive to neuroaxial anaesthesia) and was simple, flexible and acceptable to staff and patients.

Different effect of unfractionated heparin and enoxaparin on circulating proangiogenic factors during hemodialysis: A cross-over study

Background. We aimed to compare the effect of unfractionated heparin (UFH) and enoxaparin used as anticoagulants during hemodialysis (HD) on circulating levels of heparin-binding, endothelial-derived, proangiogenic factors—vascular endothelial (VEGF 165) and basic fibroblast (bFGF) growth factor. Methods. We enrolled 22 chronic HD patients, who were randomly assigned to either enoxaparin ( n = 11) or UFH ( n = 11) anticoagulation, and followed prospectively for 12 weeks before crossing over to the alternate therapy for further 12 weeks. The cytokines were measured by immunoassay at the start, at 10 and 180 min of HD. Results. The baseline VEGF 165 and bFGF levels were comparable during enoxaparin and UFH treatment. VEGF 165 significantly decreased during both enoxaparin (χ 2 ANOVA = 33.0, P < 10 −6) and UFH (χ 2 ANOVA = 27.2, P < 10 −6) anticoagulated HD, while over-HD bFGF remained stable regardless of the type of heparin. The switch from enoxaparin to UFH treatment was connected with 34% VEGF 165 decrease after 180 min of HD and had no impact on bFGF. During UFH-anticoagulated HD 75% VEGF 165 decrease after 10 min was negatively associated with heparin dosage and was more profound in patients with ischemic heart disease. Conclusion. The traditional UFH regimen, in contrast to enoxaparin treatment, is connected with dose-depended VEGF 165 decrease during HD procedure. The biological and possible clinical relevance of this observation requires further investigations.

Pharmacologic therapy for the management of thrombosis: Unfractionated heparin or low-molecular-weight heparin?

Heparin and heparin-derived drugs play a major therapeutic role in thrombotic and cardiovascular disorders. Infusion of unfractionated heparin (UFH) followed by warfarin has traditionally been the standard pharmacologic therapy for treatment of venous thromboembolism (VTE), which includes both deep vein thrombosis and pulmonary embolism, and for initial therapy of non-ST-elevation (NSTE) acute coronary syndrome (ACS). More recently, low-molecular-weight heparins (LMWHs) have been shown to provide at least as good efficacy and safety outcomes as UFH regimens for prevention of these conditions. In addition to good efficacy outcomes with LMWHs compared with UFH, LMWHs have other advantages over UFH, including improved bioavailability, QD administration, more predictable anticoagulant response, lack of the need for monitoring, and suitability for outpatient use, thereby increasing convenience, reducing cost, and improving cost-to-benefit ratios. In carefully screened and managed patients, LMWH offers a cost-effective, convenient, and safe alternative to UFH for thrombosis management. The aim of this article is to summarize efficacy, safety, and pharmacoeconomic considerations when selecting LMWH versus UFH for thrombosis management in VTE and NSTE ACS.

Anticoagulation in Hospitalized Patients With Renal Insufficiency: A Comparison of Bleeding Rates With Unfractionated Heparin vs Enoxaparin

To compare the rates of bleeding complications in patients with renal insufficiency who receive anticoagulation therapy with the full therapeutic dose, unfractionated heparin (UFH), or with twice-daily enoxaparin. A 325-bed community teaching hospital. Retrospective cohort study. The medical records of all patients with renal insufficiency who received anticoagulation therapy with UFH or enoxaparin during a 13-month period were reviewed for the occurrence of major and minor bleeding. Incidence rates were computed per 1,000-person days of anticoagulation therapy. Comparisons were made across categories of renal insufficiency and other potential confounders. A total of 620 patients with estimated glomerular filtration rates of < 60 mL/min were studied. Of these, 331 received anticoagulation therapy with UFH, 250 with enoxaparin, and 39 with both (not simultaneously). The major bleeding rates were 26.3 per 1,000 person-days for UFH and 20.7 per 1,000 person-days for enoxaparin. Major bleeding complications were similarly increased for both UFH and enoxaparin therapy across categories of worsening renal insufficiency. Patients with severe renal insufficiency while receiving enoxaparin had a 154% excess incidence of minor bleeding compared to those receiving UFH (incidence ratio, 2.54; 95% confidence interval, 1.01 to 6.36). Worsening renal insufficiency, female gender, and prolonged duration of anticoagulation therapy emerged as the main determinants for bleeding complications. Both the twice-daily enoxaparin and UFH regimens are associated with comparable increases in major bleeding complications in patients with renal dysfunction receiving full-dose anticoagulation therapy. Both agents should be used with caution in anticoagulation therapy for patients with renal insufficiency.